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Rosuvastatin Plus Ezetimibe
Abstract & Commentary
By Michael H. Crawford, MD, Professor of Medicine, and Chief of Clinical Cardiology, at the University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer.
Source: Ballantyne CM, et al. Efficacy and Safety of Rosuvastatin 40 mg Alone or in Combination with Ezetimibe in Patients at High Risk of Cardiovascular Disease (Results from the Explorer Study). Am J Cardiol. 2007;99:673-680.
Synopsis: Rosuvastatin plus ezetimibe may improve the management of high-risk patients by increasing the number that reach goal LDL cholesterol levels.
When baseline LDL cholesterol levels are high, achievement of target levels, especially < 70 mg/dl can be difficult. Thus, the EXamination of Potential Lipid-modifying effects Of Rosuvastatin in combination with Ezetimibe versus Rosuvastatin alone (EXPLORER) study was conducted at 58 centers in the U.S., Western Europe and South Africa. The purpose of this study was to compare the efficacy and safety of adding ezetimibe 10 mg to rosuvastatin 40 mg in patients with coronary artery disease (CAD) or a CHD risk equivalent profile (10-year risk > 20%) and a fasting LDL of > 160 mg/dl but < 250 mg/dl and triglycerides < 400 mg/dl. Patients were randomized to rosuvastatin alone 40 mg/day or both drugs and the primary endpoint was the percent of patients achieving an LDL < 100 mg/dl after 6 weeks of therapy. A secondary end-point was the percent achieving a non HDL cholesterol of < 130 mg/dl and high sensitivity CRP levels. Mean age of the 469 patients randomized was 63 years, just over half were men, almost 40% were diabetic and 97% had hypertension. More patients on combination therapy achieved an LDL < 100 mg/dl as compared to rosuvastatin alone (94 vs 79%, p < 0.001); the goal of < 70
mg/dl in high-risk patients (80 vs 35%, p < 0.001). Both treatments increased HDL about 10%. High sensitivity CRP levels also decreased more on combination therapy (46 vs 29%, p < 0.001). Adverse events were noted in about a third of patients with both treatments. Serous adverse events occurred in 2% or less of patients and few discontinued therapy. Myalgia was the most frequent adverse event in both groups at about 3%, but no rhabdomyolysis was observed. ALT increases were more common on combination therapy (2.5% vs 0.4%). The authors concluded that rosuvastatin plus ezetimibe may improve the management of high-risk patients by increasing the number that reach goal LDL cholesterol levels.
These results are most encouraging since 94% of these high-risk patients with mean LDL values of about 190 mg/dl achieved levels < 100, and 80% were < 70 mg/dl achieved levels < 100, and 80% were < 70 mg/dl on the combination of rosuvastatin 40 mg and ezetimibe 10 mg a day. Although comparisons to other trials are difficult because of differences in patient populations, these results are superior to those of simvastatin and atorvastatin plus ezetimibe. Also, it was reassuring that adverse events were few and not serious. No rhabdomyolysis was observed and myalgias were infrequent (3%) and the same in both treatment groups.
There were some limitations to the study. It was a short-term trial (6 weeks) and it was open-label. Of more importance there are no outcomes data. Thus, we don't know for sure that achieving aggressive LDL goals in high-risk patients by adding ezetimibe to maximum rosuvastatin therapy will improve CHD outcomes long-term.